Immunoglobulin A1 (IgA1) deposition in human tissues and organs is a characteristic of many human diseases including IgA nephropathy, Dermatitis herpetiformis (DH), and Henoch-Schoenlein purpura (HS). IgA1 deposition is responsible for a variety of clinical manifestations such as renal failure, skin blistering, rash, arthritis, gastrointestinal bleeding and abdominal pain.
There are several available treatment options for patients that present with abnormal IgA1 deposition. These include administration of corticosteroids that have immunosuppressive and anti-inflammatory properties, dietary fish oil supplements that reduce renal inflammation, and angiotensin converting enzyme inhibitors that reduce the risk of progressive renal disease and renal failure. Such treatments do not directly act on IgA1 deposits in tissue or organs.
To address this issue of IgA1 deposit removal, exogenous proteolytic enzymes have been tested in IgA1 deposition animal models (Gesualdo L. et al, (1990) J. Clin. Invest. 86: 715-722 and Nakazawa M. et al. (1986) J. Exp. Med 164: 1973-1987). The proteases, chymopapain and subtilisin, act by proteolytic cleavage of IgA1 deposits in the kidney but are not specific for IgA1 molecules and will digest a variety of other proteins.
Thus, despite advances in the field, there is a need in the art for therapeutic agents that can be used to treat IgA1 deposition diseases.